TMEFF2

protein-coding

transmembrane protein with EGF like and two follistatin like domains 2

Gene summary

This gene encodes a member of the tomoregulin family of transmembrane proteins. This protein has been shown to function as both an oncogene and a tumor suppressor depending on the cellular context and may regulate prostate cancer cell invasion. Multiple soluble forms of this protein have been identified that arise from both an alternative splice variant and ectodomain shedding. Additionally, this gene has been found to be hypermethylated in multiple cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

MANE transcript

NM_016192.4

Inheritance

—

ClinVar variants

U:18B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr2:191,949,043-192,194,933

External References & Databases

Ensembl (ENSG00000144339)

Transcript & Mutation Effects

hg38 • Region Span ~245.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEFF2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 18

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016192.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			18 clinvar		1 clinvar	19
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	18	0	1	19

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016192.4	RefSeq	NP_057276.2	10	MANE Select
ENST00000272771.10	Ensembl	ENSP00000272771.5	10	MANE Select
NM_001305134.2	RefSeq	NP_001292063.1	10	Standard
NM_001305145.1	RefSeq	NP_001292074.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Validated targets of C-MYC transcriptional repression

Biological Process

negative regulation of cell migration
wound healing, spreading of cells
negative regulation of integrin biosynthetic process
negative regulation of stress fiber assembly

Molecular Function

molecular_function

Cellular Component

extracellular region
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000272771
Coding exons: 10
Length: 246667
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	140	204	0.685	0.00000985	2465
Missense (PolyPhen)		40	65.206	0.61344		758
Synonymous	0.792	70	79.0	0.887	0.00000431	672
Loss of Function	2.54	11	24.6	0.447	0.00000129	274

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be a survival factor for hippocampal and mesencephalic neurons. The shedded form up-regulates cancer cell proliferation, probably by promoting ERK1/2 phosphorylation. {ECO:0000269|PubMed:10903839, ECO:0000269|PubMed:17942404}.;

Recessive Scores

pRec: 0.262

Intolerance Scores

LoFtool: 0.420
RVIS EVS: -0.14
RVIS percentile EVS: 43.29

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium